In vivo genotoxicity evaluation of cylindrospermopsin in rats using a combined micronucleus and comet assay

Díez-Quijada, Leticia; Llana-Ruiz-Cabello, María; Cătunescu, Giorgiana M.; Puerto, María; Moyano, Rosario; Jos, Ángeles; Cameán, Ana M.

doi:10.1016/j.fct.2019.110664

Cited by 24 publications

(32 citation statements)

References 55 publications

(85 reference statements)

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“…Overall in this study, using rats as experimental model, the CYN/MC-LR combinations increased the % MN-PCE in bone marrow cells, although it induced no DNA strand breaks nor any oxidative DNA damage in any of the investigated tissues. These results are in accordance with the only two previous genotoxicity in vivo assay carried out in rats with pure individual toxins: CYN alone under the same combined assays [43] and MC-LR administered i.v. through the comet assay [28].…”

Section: Discussionsupporting

confidence: 92%

“…through the comet assay [28]. Generally, the results of this study show no synergism or antagonism between CYN and MC-LR in the assayed combinations and concentrations in rats, because the effects are similar to the in vivo exposure to CYN alone [43]. Moreover, these findings confirm the in vitro experiments performed with the CYN/MC-LR mixture through a battery of tests, in which MN and comet assays were included [49].…”

Section: Discussionsupporting

confidence: 84%

“…It combines and relates the results of the two types of comet assays (standard and enzyme-modified) on cells isolated from stomach, liver, and blood, with the MN test in bone marrow cells. The assays were performed according to the OECD 489 and 474 guidelines, respectively [53,54] with some alterations, as described by Diez-Quijada et al [43]. The combined comet-MN assay [58] reduces the use of animals according to the 3Rs principles (Replace, Reduce, and Refine), and it increases the sensitivity and specificity of the assays, decreasing the number of false negative results [59].…”

Section: Discussionmentioning

confidence: 99%

“…CYN exposure doses (75, 23.7, and 7.5 µg/kg b.w.) were selected according to a previous in vivo study performed with the individual toxin [43]. The doses of MC-LR were 10 times higher than CYN because of its proportionally higher abundance in the environment [64].…”

Section: Discussionmentioning

confidence: 99%

“…to CYN and to an extract of Cylindrospermopsis raciborskii. Recently, Diez-Quijada et al [43] exposed rats to pure CYN (7.5-75.0 µg/kg b.w) and performed a battery of assays consisting of MN in bone marrow, as well as the standard and modified comet assays in stomach, liver and blood. The DNA seemed to be damaged only in the bone marrow of rats regardless of concentration.…”

Section: Introductionmentioning

confidence: 99%

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Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats

Díez-Quijada

Medrano-Padial

Llana-Ruiz-Cabello

et al. 2020

Toxins

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Cylindrospermopsin (CYN) and microcystins (MC) are cyanotoxins that can occur simultaneously in contaminated water and food. CYN/MC-LR mixtures previously investigated in vitro showed an induction of micronucleus (MN) formation only in the presence of the metabolic fraction S9. When this is the case, the European Food Safety Authority recommends a follow up to in vivo testing. Thus, rats were orally exposed to 7.5 + 75, 23.7 + 237, and 75 + 750 μg CYN/MC-LR/kg body weight (b.w.). The MN test in bone marrow was performed, and the standard and modified comet assays were carried out to measure DNA strand breaks or oxidative DNA damage in stomach, liver, and blood cells. The results revealed an increase in MN formation in bone marrow, at all the assayed doses. However, no DNA strand breaks nor oxidative DNA damage were induced, as shown in the comet assays. The histopathological study indicated alterations only in the highest dose group. Liver was the target organ showing fatty degeneration and necrotic hepatocytes in centrilobular areas, as well as a light mononuclear inflammatory periportal infiltrate. Additionally, the stomach had flaking epithelium and mild necrosis of epithelial cells. Therefore, the combined exposure to cyanotoxins may induce genotoxic and histopathological damage in vivo.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats

Díez-Quijada

Medrano-Padial

Llana-Ruiz-Cabello

et al. 2020

Toxins

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DNA damage induced by cylindrospermopsin on different tissues of the biomonitor fish Poecilia reticulata

Rabelo

Hanusch

Jesus

et al. 2021

Environmental Toxicology

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The cyanotoxin cylindrospermopsin (CYN) is the second biggest cause of poisoning worldwide, both in humans and animals. Although CYN primarily affects the aquatic environments and can be absorbed in fishes by multiple routes, data reporting its toxicity and mechanism of action are still scarce in this group. Using P. reticulata as model species, it was evaluated whether CYN promotes mutagenic and genotoxic effects in different fish target tissues. Adult females were exposed in a static way to 0 (control), 0.5, 1.0, and 1.5 μg L −1 of pure CYN for 24 and 96 hours. For the first time, DNA damage was detected in fish brain after CYN exposition. In brain cells, a concentrationresponse DNA damage was observed for both exposure times, suggesting a direct or indirect action of CYN in neurotoxicity. For the liver cells, 96 hours caused an increase in DNA damage, as well the highest percentage of DNA in the tail was reached when used 1.5 μg L −1 of CYN. In peripheral blood cells, an increase in DNA damage was observed for all tested concentrations after 96 hours. In erythrocytes, micronuclei frequency was higher at 1.5 μg L −1 treatment while the erythrocyte nuclear abnormalities (ENA) frequency was significantly higher even at the lowest CYN concentration. Such data demonstrated that acute exposition to CYN promotes genotoxicity in the brain, liver, and blood cells of P. reticulata, as well mutagenicity in erythrocytes. It rises an alert regarding to the toxic effects of CYN for aquatic organisms as well as for human health.

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Genotoxicity of Cyanotoxins

Sadeepa,

Bandara,

Liyanage

et al. 2023

Protocols for Cyanobacteria Sampling and Detection of Cyanotoxin

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In vivo genotoxicity evaluation of cylindrospermopsin in rats using a combined micronucleus and comet assay

Cited by 24 publications

References 55 publications

Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats

Cylindrospermopsin-Microcystin-LR Combinations May Induce Genotoxic and Histopathological Damage in Rats

DNA damage induced by cylindrospermopsin on different tissues of the biomonitor fish Poecilia reticulata

Genotoxicity of Cyanotoxins

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